HIV-1 infection continues to remain a major global public health problem and it is now spreading in the highly populated countries of South East Asia. India, with a population of over 1 billion, has been reported to have over 5 million infected individuals. According to figures available from the Government of India, all states in the country now have HIV-1 infection. The infecting HIV-1 clade in India is mostly clade C rather than clade B which is prevalent in the West. Progression of HIV is dependent upon various factors including the clade of the virus as well as host genetics. However, what we know about these relationships is the result of investigations carried out in relation to only clade B virus. In the present application we propose to assess the relationship between host genetic polymorphism and HIV coreceptor expression on progression of HIV-1 C clade disease and how these factors subsequently affect NP impairment through their effects on disease progression determined by enumerating CD4 cells and measuring the viral load. Information regarding the progression of clade C infection and its neuro-effects is essential in order to make strategies for public health intervention. We therefore propose to investigate longitudinally 200 HIV-1 + (with clade C), community residing men and women in Chandigarh area in North India. These individuals will be investigated for plasma viral loads and CD4 cells and expression of CCR5 and CXCR4 coreceptors; and, CCR5 gene variants on CD4 cells, as well as neurocognitive status with the following aims: 1.(a): To determine annually the surface expression of CCR5 and CXCR4 on CD4 cells of infected individuals. 1 .(b): To determine the impact of host genetics on the progression of HIV-1 clade C infection using polymorphism of clade C co-receptor genes. 2. To evaluate the prevalence and longitudinal progression of neuropsychological impairment among HIV-1 + participants. 3. To investigate the relationships of findings from Aim 1(a) and 1(b) on cognitive impairments delineated in Aim 2. An annual neurocognition evaluation will also be carried out with an SES matched seronegative group (N=100) in order to rule out any practice effects due to repeated neuropsychological testing.The findings will help in generalizing the overall role of host genetics and polymorphism of co-receptors on the progression and neurocognitive deficits occurring in HIV-1 infection. [unreadable] [unreadable] [unreadable]